The scientists modified the genes of the mice so that the cells lining their respiratory systems had a human version of a "receptor protein".
By: Steve Connor, Science Editor
Monday, 4 February 2008

For fifty years researchers have tried and failed to find a cure for the common cold. But now scientists are claiming a significant breakthrough that could herald the development of new treatments and drugs to prevent the scourge of the nasal passages.

They announced yesterday that they had been able to pass on the virus to a special strain of genetically modified mice the first time a non-primate has caught a cold.

Until now, only humans and chimpanzees were known to be susceptible to the virus that results in the common cold. This is one of the reasons why research into possible cures has been so slow, according to Professor Sebastian Johnston, a virologist at Imperial College London who led the mouse research. Being able to infect laboratory mice with rhinoviruses the main group of common cold viruses means scientists can now investigate how the virus infects an animal other than a human being, which could speed up the rate at which new drugs are developed, Professor Johnston said.

About three quarters of people with common colds, which are not to be confused with influenza, are infected with one of the more than 100 rhinoviruses. Most people shrug off colds within a few days but in some people with respiratory problems such as asthma a cold can be fatal.

Colds can result in babies and small children being admitted to hospital, lead to pneumonia in people with weakened immune systems and can trigger asthma attacks. They can also cause acute attacks of chronic bronchitis and emphysema, sometimes with fatal consequences.

In 1946, the Medical Research Council set up the Common Cold Unit in Wiltshire where 30 human volunteers at a time were infected with cold viruses to study how their bodies responded to the infection over a period of about 10 days. The unit was closed in 1989 after failing to find a cure.

Professor Johnston said: "Until now, it has not been possible to study rhinovirus infection in small animals. This has been a major obstacle to developing new treatments and there is currently no effective treatment for rhinovirus infection.

"Rhinoviruses are a major cause of the common cold and if you have a small animal model, it speeds up the rate of discovering new potential treatments. And rhinoviruses are not innocent viruses. They kill people in large numbers from acute asthma attacks and chronic bronchitis and emphysema," Professor Johnston added.

The scientists, who were funded by the Medical Research Council, modified the genes of the mice so that the cells lining their respiratory systems had a human version of a "receptor protein" called ICAM-1, which rhinoviruses use to infect the cells.

"We previously found that once inside the mouse cell a rhinovirus reproduces itself as well as it does in human cells. But the virus couldn't infect the mouse cell because the receptor which acts like a door key wouldn't let the virus into the cell.

"Now we've modified the mouse receptor so it is more like a human one. This means the virus can infect the cells of these modified mice. We found that mice with the modified receptor were susceptible to infection with a rhinovirus," he said.

The study, which is published in the journal Nature Medicine, will also prove important in the understanding of life-threatening respiratory attacks resulting from acute asthma, bronchitis and other serious lung infections.

Professor Johnston said that the genetically modified strain of mouse he and his colleagues had created could also be used to study what happens during these more dangerous infections when the function of the lung is threatened and people can die as a result.

"If combined with an allergen such as the protein found in egg white that could cause an allergic reaction in the lungs, the virus could make the response worse and lead to an 'asthma attack'.

"These mouse models should provide a major boost to research efforts to develop new treatments for the common cold, as well as for more potentially fatal illnesses such as acute attacks of asthma and of chronic obstructive pulmonary disease," he said.

The research was funded by the Medical Research Council and the charity Asthma UK.

The chief executive of the Medical Research Council, Professor Sir Leszek Borysiewicz, said: "This important and fundamental discovery will enable us to understand the effects rhinoviruses and common colds have on our health.

"It will open up new paths to finding treatments which have been delayed for many years and provides us with the opportunities for further breakthroughs in the future."

Leanne Male, assistant director of research at Asthma UK, said: ''Ninety per cent of people with asthma tell us that colds and flu trigger their asthma symptoms but as yet there is no specific treatment for virally induced asthma attacks and steroid treatments are only partially effective against them.

"We welcome this latest advancement as it will lead to a greater understanding of viral infections and their link with asthma and may help the development of a suitable treatment for virus-induced asthma attacks, thus greatly improving the lives of the 5.2 million people with the condition in the UK."